Jacobs M, Brown N, Allie N, Ryffel B
Department of Immunology, University of Cape Town, Cape Town, South Africa.
Clin Immunol. 2000 Mar;94(3):192-9. doi: 10.1006/clim.2000.4835.
Neutralization of TNF or disruption of TNF-R1 leads to fatal Mycobacterium bovis BCG infection. Here we used TNF-LT-alpha-deficient mice to test whether a complete disruption of TNF and LT-alpha reduces further host resistance to BCG infection. The bacterial burden especially in the lungs of TNF-LT-alpha-deficient mice was significantly increased and the mice succumbed to infection between 8 and 10 weeks. In the absence of TNF-LT-alpha the granulomatous response was severely impaired and delayed. The cells in the granulomas of TNF-LT-alpha-deficient mice expressed low levels of MHC class II and ICAM-1. They contained a few T cells and F4/80-positive macrophages expressing little iNOS and acid phosphatase activity. By contrast, the lethal action of endotoxin was dramatically reduced in BCG-infected TNF-LT-alpha-deficient mice. In summary, in the absence of TNF-LT-alpha the recruitment and activation of mononuclear cells in response to BCG infection were significantly delayed and reduced resulting in immature granulomas allowing uncontrolled fatal infection.
肿瘤坏死因子（TNF）的中和或肿瘤坏死因子受体1（TNF-R1）的破坏会导致致命的牛分枝杆菌卡介苗（BCG）感染。在此，我们使用缺乏TNF-LT-α的小鼠来测试TNF和LT-α的完全缺失是否会进一步降低宿主对BCG感染的抵抗力。细菌负荷，尤其是在缺乏TNF-LT-α的小鼠肺部，显著增加，并且这些小鼠在8至10周内死于感染。在没有TNF-LT-α的情况下，肉芽肿反应严重受损且延迟。缺乏TNF-LT-α的小鼠肉芽肿中的细胞表达低水平的主要组织相容性复合体II类分子（MHC class II）和细胞间黏附分子-1（ICAM-1）。它们含有少量T细胞和F4/80阳性巨噬细胞，这些巨噬细胞表达很少的诱导型一氧化氮合酶（iNOS）和酸性磷酸酶活性。相比之下，在感染BCG的缺乏TNF-LT-α的小鼠中，内毒素的致死作用显著降低。总之，在没有TNF-LT-α的情况下，对BCG感染的单核细胞募集和激活显著延迟且减少，导致肉芽肿不成熟，从而允许不受控制的致命感染。
